chr19-6721629-A-C

Variant names:

• chr19-6721629-A-C
• rs11569393
• ENST00000600744.1:c.-50+1812T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600744.1(C3):​c.-50+1812T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,904 control chromosomes in the GnomAD database, including 12,168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (12168 hom., cov: 32)
• Consequence: C3 ENST00000600744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729
• Publications: 2 publications found

Genes affected

C3 (HGNC:1318): (complement C3) Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]

C3 Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with C3 anomaly

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• complement component 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
• C3 glomerulonephritis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000600744.1	c.-50+1812T>G		intron_variant	Intron 2 of 3	5		ENSP00000472044.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55280 AN: 151786 Hom.: 12166 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.379

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55278 AN: 151904 Hom.: 12168 Cov.: 32 AF XY: 0.364 AC XY: 27027 AN XY: 74194

African (AFR) AF: 0.124 AC: 5124 AN: 41418

American (AMR) AF: 0.333 AC: 5082 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3468

East Asian (EAS) AF: 0.189 AC: 977 AN: 5176

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4814

European-Finnish (FIN) AF: 0.522 AC: 5487 AN: 10504

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34084 AN: 67956

Other (OTH) AF: 0.378 AC: 798 AN: 2110

Alfa AF: 0.422 Hom.: 3818

Bravo AF: 0.339

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.75
PhyloP100		0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11569393; hg19: chr19-6721640;